THE EFFECTS OF AGE AND GENDER ON THE SINGLE-DOSE PHARMACOKINETICS OF AVITRIPTAN ADMINISTERED TO HEALTHY-VOLUNTEERS

The effects of age and gender on the single dose pharmacokinetics of a vitriptan and its three metabolites were assessed in 15 young men, 15 young women, 15 elderly men and 15 elderly women. Avitriptan was admin istered as a 150-mg capsule after a 10-hour fast and serial plasma and urine samples were collected up to 36 hours after the dose. Plasma sa mples were analyzed for avitriptan and its metabolites, N-desmethyl av itriptan (ND048), O-desmethyl avitriptan (OD048) and methoxypyrimidiny l piperazine (MPP). Urine samples were analyzed for only avitriptan an d MPP. Avitriptan was well tolerated in all four groups. The drug was rapidly absorbed with a median time to maximum plasma concentration (t (max)) between 0.5 and 1.5 hours. No significant gender-related differ ences were found in the maximum plasma concentration (C-max) and area under the concentration-time curve extrapolated to infinity (AUC(0-inf inity)) of avitriptan. Renal clearance of avitriptan was significantly smaller in young women compared with young men, but this is clinicall y not relevant because only 2% to 3% of the total dose is excreted unc hanged. Compared with the young volunteers, mean C-max was approximate ly 50% higher in the elderly but there was no difference in the AUC(0- infinity) between the 2 age groups. Plasma concentrations of ND048, OD 048, and MPP were each 50 to 100 fold lower than those of avitriptan. Hence some age-and gender-related differences found in the pharmacokin etics of avitriptan metabolites are probably not relevant in the asses sment of overall safety and efficacy of avitriptan. Based on the pharm acokinetics and tolerability, no age or gender-related dose adjustment is necessary for avitriptan.